The human placenta, until recently thought to be an immunologically inert organ, has been found to be a very rich source for lymphokine production. We have been able to produce Interleukin-1 (IL-1), a stimulatory lymphokine, in very high titer from cultured placental cells. In addition, we have isolated factor(s) with strong suppressive activity for PHA and MLC responses. This suppressive activity has been characterized preliminarily as a protein with molecular weight 60-80,000 daltons. The findings raise the possibility that this potential for immune activity in the placenta may play a role in the maintenance of the normal materno-fetal relationship, and that abnormal regulation of lymphokine production may be included in various pathophysiological conditions of pregnancy. Investigation of these lymphokines will focus on four areas: (1) Basic immunobiology (cell(s) of origin, physiologic inducers, mechanisms of action); (2) Comparative development and pathology (lymphokine production in normal and abnormal placentas and at varying gestational ages); (3) Characterization and partial purification (physiochemical characteristics, gel filtration, isoelectric focusing); and (4) Development of monoclonal and anti-suppressor lymphokine antibodies (a tool to assist purification, functional studies, and potentially replace bioassay). The ability to extract large quantities of lymphokines from the placenta will be a major advantage for these studies. Most other investigations of human lymphokine biology have been significantly restricted by the limited availability of substrate. A more complete understanding of placental lymphokine function will aid our understanding both of maternal-fetal tolerance and of placental function in normal and abnormal pregnancies.